Chitosan and its use

Abstract

This invention discloses a chitosan, its applications, and a preparation method. The chitosan is α-chitosan or β-chitosan, and has a specific molecular weight and degree of deacetylation. The chitosan of this invention can be used to prepare products for the prevention or treatment of gastrointestinal mucosal damage.

Description

Technical Field

[0001] This invention relates to the pharmaceutical field, specifically to a chitosan and its applications, and more specifically to a chitosan and its application in the prevention or treatment of diseases involving damage to the gastrointestinal mucosa. Background Technology

[0002] Gastrointestinal mucosal injury is a common digestive system disorder and a key factor in the development of various gastrointestinal diseases, including gastric mucosal injury, gastritis, gastric ulcers, intestinal mucosal injury, duodenal ulcers, enteritis, or ulcerative colitis. Factors causing gastrointestinal mucosal injury include chemical factors (smoking, alcohol, strong tea, coffee, and medications that irritate the gastric mucosa, such as aspirin and indomethacin), physical factors (excessively cold, hot, or rough foods, or overeating), bacterial infections, or other toxin irritation.

[0003] Chitosan, a product of chitin after deacetylation, exists in three types: α-, β-, and γ-. It is a non-toxic polysaccharide with excellent biological activity. Chitosan can neutralize stomach acid, inhibit the growth of Helicobacter pylori, and form a thin film to cover damaged mucosa, preventing further damage and irritation to the gastrointestinal mucosa. Some hydrolysis products of chitosan are bioactive substances essential for the growth of epidermal cells or tissues, promoting the formation of granulation tissue and new blood vessels in ulcer areas. Based on these effects, chitosan can be used to prevent or treat gastrointestinal mucosal damage.

[0004] Existing studies have reported that the antibacterial effect or protective effect of chitosan on the gastric mucosa may be related to its molecular weight, degree of deacetylation, and crystal form.

[0005] Reference 1 discloses the antibacterial experiment of two chitosans with different degrees of deacetylation (70% and 88.5%) against Helicobacter pylori. Among them, chitosan with a lower degree of deacetylation showed stronger antibacterial activity. Reference 1 only studied the effect of the degree of deacetylation on the antibacterial activity of chitosan, and did not study the effect of molecular weight and crystal form.

[0006] Reference 2 compared the preventive and therapeutic effects of low molecular weight chitosan (molecular weight: 20,000-50,000 Da, degree of deacetylation: 90.2%) and high molecular weight chitosan (molecular weight: 500,000 to 1,000,000 Da, degree of deacetylation: 82.0%) on gastric mucosal damage induced by ethanol or acetic acid in rats, and found that low molecular weight chitosan had a stronger protective effect on the gastric mucosa.

[0007] Reference 3 discloses that a gel containing high molecular weight chitosan with a molecular weight of 500-700 kDa and a degree of deacetylation of 80% and dextropanthenol can be used to prevent gastric mucosal ulcers. Reference 4 prepares a chitosan with a molecular weight of over 1.5 million and a degree of deacetylation of over 98%, which can be compounded with other components to make an active biomimetic material containing chitosan for repairing gastric mucosa.

[0008] References 2-4 did not disclose the crystal form of the chitosan, nor did they study the effect of the crystal form of chitosan on the protective effect on the gastric mucosa.

[0009] Although existing technologies have disclosed various chitosans with different molecular weights and degrees of deacetylation that can inhibit Helicobacter pylori or protect the gastrointestinal mucosa, the molecular weight, degree of deacetylation, and crystal form of chitosan and their protective effects on the gastrointestinal mucosa have not yet been clearly defined. There remains a need in this field to develop more effective chitosans for use as gastrointestinal mucosal protectants.

[0010] Document 1 CN 1660128 A

[0011] Reference 2 JP1997221427 A

[0012] Reference 3 RU2759575 C1

[0013] Reference 4 CN 101116754 A Summary of the Invention

[0014] This invention has found that the efficacy of chitosan in preventing or treating gastrointestinal mucosal damage is related to its molecular weight, degree of deacetylation, or crystal form. This invention provides chitosan with specific molecular weight, degree of deacetylation, and crystal form, which can be used to prevent or treat gastrointestinal mucosal damage.

[0015] In a first aspect, the present invention provides a chitosan, wherein the chitosan has at least one of the following characteristics:

[0016] (1) The molecular weight of the chitosan is 5-400 kDa;

[0017] (2) Deacetylation degree greater than 85%;

[0018] (3) The chitosan is α-chitosan or β-chitosan;

[0019] (4) The chitosan is used to prepare products for the prevention or treatment of gastrointestinal mucosal damage.

[0020] Preferably, the chitosan possesses at least one of the following characteristics:

[0021] (1) The molecular weight of the chitosan is 10-300 kDa;

[0022] (2) Deacetylation degree greater than 90%;

[0023] (3) The chitosan is α-chitosan or β-chitosan;

[0024] (4) The chitosan is used to prepare products for the prevention or treatment of gastrointestinal mucosal damage.

[0025] Preferably, the chitosan possesses at least one of the following characteristics:

[0026] (1) The molecular weight of the chitosan is 20-140 kDa;

[0027] (2) Deacetylation degree greater than 90%;

[0028] (3) The chitosan is α-chitosan or β-chitosan;

[0029] (4) The chitosan is used to prepare products for the prevention or treatment of gastrointestinal mucosal damage.

[0030] This invention investigated the efficacy of different crystalline forms of chitosan in preventing or treating gastrointestinal mucosal damage. It found that the efficacy of different crystalline forms of chitosan is closely related to their molecular weight, with different crystalline forms exhibiting significantly better efficacy within different molecular weight ranges. Furthermore, this invention also found that α-chitosan has better efficacy than β-chitosan.

[0031] In some embodiments of the present invention, the chitosan is α-chitosan with a molecular weight of 60-200 kDa, preferably 70-140 kDa; more preferably 80-140 kDa.

[0032] In some embodiments of the present invention, the chitosan is β-chitosan with a molecular weight of 10-350 kDa, preferably with a molecular weight of 20-100 kDa, and more preferably with a molecular weight of 20-50 kDa.

[0033] The present invention further investigated the effect of the degree of deacetylation of chitosan on its prevention or treatment of gastrointestinal mucosal damage. The present invention found that when the degree of deacetylation of chitosan is greater than 90%, the chitosan has a more significant therapeutic effect, especially a more significant effect in preventing gastrointestinal mucosal damage.

[0034] As a preferred embodiment, the present invention also provides a chitosan, wherein the chitosan has at least one of the following characteristics:

[0035] (1) The molecular weight of the chitosan is 60-200 kDa;

[0036] (2) Deacetylation degree greater than 90%;

[0037] (3) The chitosan is α-chitosan;

[0038] (4) The chitosan is used to prepare products for the prevention or treatment of gastrointestinal mucosal damage.

[0039] In a preferred embodiment of the present invention, the chitosan has at least one of the following characteristics:

[0040] (1) The molecular weight of the chitosan is 70-140 kDa;

[0041] (2) Deacetylation degree greater than 90%;

[0042] (3) The chitosan is α-chitosan;

[0043] (4) The chitosan is used to prepare products for the prevention or treatment of gastrointestinal mucosal damage.

[0044] In a preferred embodiment of the present invention, the chitosan has a molecular weight of 70-140 kDa and a degree of deacetylation greater than 90%; the chitosan is α-chitosan; and the chitosan is used to prepare products for the prevention or treatment of gastrointestinal mucosal damage.

[0045] In a preferred embodiment of the present invention, the chitosan has a molecular weight of 80-140 kDa and a degree of deacetylation greater than 90%; the chitosan is α-chitosan; and the chitosan is used to prepare products for the prevention or treatment of gastrointestinal mucosal damage.

[0046] In a preferred embodiment of the present invention, the chitosan has at least one of the following characteristics:

[0047] (1) The molecular weight of the chitosan is 10-350 kDa;

[0048] (2) Deacetylation degree greater than 90%;

[0049] (3) The chitosan is β-chitosan;

[0050] (4) The chitosan is used to prepare products for the prevention or treatment of gastrointestinal mucosal damage.

[0051] In a preferred embodiment of the present invention, the chitosan has at least one of the following characteristics:

[0052] (1) The molecular weight of the chitosan is 20-100 kDa;

[0053] (2) Deacetylation degree greater than 90%;

[0054] (3) The chitosan is β-chitosan;

[0055] (4) The chitosan is used to prepare products for the prevention or treatment of gastrointestinal mucosal damage.

[0056] In a preferred embodiment of the present invention, the chitosan has at least one of the following characteristics:

[0057] (1) The molecular weight of the chitosan is 20-50 kDa;

[0058] (2) Deacetylation degree greater than 90%;

[0059] (3) The chitosan is β-chitosan;

[0060] (4) The chitosan is used to prepare products for the prevention or treatment of gastrointestinal mucosal damage.

[0061] In a preferred embodiment of the present invention, the chitosan has a molecular weight of 20-50 kDa and a degree of deacetylation greater than 90%; the chitosan is β-chitosan; and the chitosan is used to prepare products for the prevention or treatment of gastrointestinal mucosal damage.

[0062] In a second aspect, the present invention provides the use of chitosan in the preparation of products for the prevention or treatment of gastrointestinal mucosal damage, wherein the chitosan possesses at least one of the following characteristics:

[0063] (1) Molecular weight is 5-400 kDa;

[0064] (2) Deacetylation degree greater than 85%;

[0065] (3) The chitosan is α-chitosan or β-chitosan.

[0066] In a preferred embodiment, the present invention provides the use of chitosan in the preparation of products for the prevention or treatment of gastrointestinal mucosal damage, wherein the chitosan possesses at least one of the following characteristics:

[0067] (1) Molecular weight is 10-300 kDa;

[0068] (2) Deacetylation degree greater than 90%;

[0069] (3) The chitosan is α-chitosan or β-chitosan.

[0070] As a preferred embodiment, the present invention provides the use of chitosan in the preparation of products for the prevention or treatment of gastrointestinal mucosal damage, wherein the chitosan is α-chitosan with a molecular weight of 60-200 kDa; preferably, the molecular weight of the α-chitosan is 70-140 kDa; more preferably, the molecular weight of the α-chitosan is 80-140 kDa.

[0071] As a preferred embodiment, the present invention provides the use of chitosan in the preparation of products for the prevention or treatment of gastrointestinal mucosal damage, wherein the chitosan is α-chitosan with a molecular weight of 60-200 kDa and a degree of deacetylation greater than 90%; preferably, the molecular weight of the α-chitosan is 70-140 kDa and the degree of deacetylation is greater than 90%; preferably, the molecular weight of the α-chitosan is 80-140 kDa and the degree of deacetylation is greater than 90%.

[0072] As a preferred embodiment, the present invention provides the use of chitosan in the preparation of products for the prevention or treatment of gastrointestinal mucosal damage, wherein the chitosan is β-chitosan with a molecular weight of 10-350 kDa; preferably, the molecular weight of the β-chitosan is 20-100 kDa; more preferably, the molecular weight of the β-chitosan is 20-50 kDa.

[0073] As a preferred embodiment, the present invention provides the use of chitosan in the preparation of products for the prevention or treatment of gastrointestinal mucosal damage, wherein the chitosan is β-chitosan with a molecular weight of 10-350 kDa and a degree of deacetylation greater than 85%; preferably, the β-chitosan has a molecular weight of 20-100 kDa and a degree of deacetylation greater than 90%; more preferably, the β-chitosan has a molecular weight of 20-50 kDa and a degree of deacetylation greater than 90%.

[0074] The diseases described in this invention include acute gastric mucosal injury, gastritis, gastric ulcer, intestinal mucosal injury, duodenal ulcer, enteritis, ulcerative colitis, or digestive system ulcers, etc.

[0075] As a preferred embodiment, the present invention provides the use of chitosan in the preparation of products for preventing gastrointestinal mucosal damage.

[0076] As a preferred embodiment, the present invention provides the use of chitosan in the preparation of products for preventing gastrointestinal mucosal damage, wherein the chitosan is α-chitosan with a molecular weight of 80-140 kDa and a degree of deacetylation greater than 90%.

[0077] As a preferred embodiment, the present invention provides the use of chitosan in the preparation of products for preventing gastrointestinal mucosal damage, wherein the chitosan is β-chitosan with a molecular weight of 20-100 kDa and a degree of deacetylation greater than 90%.

[0078] As a preferred embodiment, the present invention provides the use of chitosan in the preparation of products for preventing gastric ulcers.

[0079] As a preferred embodiment, the present invention provides the use of chitosan in the preparation of products for preventing gastric ulcers, wherein the chitosan is α-chitosan with a molecular weight of 80-140 kDa and a degree of deacetylation greater than 90%.

[0080] As a preferred embodiment, the present invention provides the use of chitosan in the preparation of products for preventing gastric ulcers, wherein the chitosan is β-chitosan with a molecular weight of 20-100 kDa and a degree of deacetylation greater than 90%.

[0081] The products described in this invention are not particularly limited and can be any kind of medicine, health product, food, beverage, etc.

[0082] The product of this invention may also contain excipients when necessary. If prepared as a pharmaceutical, the excipients are pharmaceutically acceptable; if prepared as a food, the excipients are food-acceptable.

[0083] As a preferred embodiment of the present invention, the pharmaceutically acceptable excipients include one or more of the following: fillers, excipients, wetting agents, flow aids, disintegrants, binders, plasticizers, antioxidants, antibacterial agents, emulsifiers, solubilizers, osmotic pressure regulators, surfactants, or pH regulators.

[0084] The product includes solid or liquid preparations; preferably, the product includes tablets, capsules, granules, powders, pills, powders, gels, or solutions.

[0085] In another aspect, the present invention provides a method for preparing chitosan, the method comprising the following steps: reacting high molecular weight chitosan with peroxide in an acidic solution. The high molecular weight chitosan is chitosan with a molecular weight greater than 200 kDa, preferably higher than 300 kDa.

[0086] In a specific embodiment of the present invention, the chitosan is β-chitosan, the molecular weight of the β-chitosan is 20-100 kDa, and the degree of deacetylation is greater than 90%. The method includes the following steps: reacting high molecular weight β-chitosan with peroxide in an acidic solution to obtain it.

[0087] In a specific embodiment of the present invention, the chitosan is α-chitosan, the molecular weight of the α-chitosan is 70-140 kDa, and the degree of deacetylation is greater than 90%. The method includes the following steps: reacting high molecular weight α-chitosan with peroxide in an acidic solution to obtain it.

[0088] In the method, the acidic solution is a hydrochloric acid solution with a concentration of 6.0% or less; preferably, the hydrochloric acid concentration is 5.0% or less; more preferably, the hydrochloric acid concentration is 4.0% or less; and more preferably, the hydrochloric acid concentration is 0.05-4.0%.

[0089] The reaction time is 0.5-6.0 hours, with a preferred reaction time of 1.0-5.0 hours.

[0090] The reaction temperature is 30-80℃, and the preferred reaction temperature is 35-70℃.

[0091] The peroxide is hydrogen peroxide, with a concentration of 10% or higher, preferably 20% or higher. Attached Figure Description

[0092] Figure 1 Powder X-ray diffraction pattern of α-chitosan sample.

[0093] Figure 2 Powder X-ray diffraction pattern of β-chitosan sample. Detailed Implementation

[0094] The following specific examples are used to further illustrate the concept of the present invention and should not be construed as limiting the invention. Unless otherwise specified, the reagents, starting materials, solution preparations, etc. used in the present invention can all be obtained commercially or prepared or carried out by methods known in the art.

[0095] Test method:

[0096] The degree of deacetylation described in this invention is determined by potentiometric titration.

[0097] The "molecular weight" mentioned in this invention refers to the weight-average molecular weight. This invention employs a multi-angle laser light scattering detector and a differential refractive index detector in combination to determine the weight-average molecular weight and molecular weight distribution of chitosan. The test conditions are as follows:

[0098] Chromatographic conditions: Column: TSKgel G5000PWxl, 7.8mm × 300mm (with guard column, TSKguardcolumn PWxl, 6.0mm × 40mm); Mobile phase: 0.15mol / L ammonium acetate, pH adjusted to 4.5 with acetic acid (11.562g ammonium acetate dissolved in 1000ml water, pH adjusted to 4.5 with acetic acid), filtered through a 0.22μm filter membrane; Column temperature: 30℃; Flow rate: 0.5ml / min; Injection volume: 30μl; Detector: Differential refractive index detector coupled with multi-angle laser scattering instrument; Isocratic run: 35 minutes.

[0099] Solution preparation: Blank solvent: mobile phase; Test solution: Take an appropriate amount of this product, add the mobile phase to dissolve and dilute to prepare a solution containing about 3.5 mg per 1 ml, shake and let stand overnight.

[0100] Determination: Accurately measure the blank solvent and the test solution respectively. The sample was injected into the liquid chromatograph, and the chromatogram was recorded. The weight-average molecular weight and molecular weight distribution of the sample were calculated using ASTRA software.

[0101] The refractive index increment dn / dc is temporarily referenced to polysaccharides and calculated using 0.1380.

[0102] Example 1 Preparation of α-Chitosan Sample 1

[0103] The starting material was α-chitosan. First, the α-chitosan was pulverized, and the pulverized α-chitosan powder was sieved to obtain uniformly sized α-chitosan powder. 10.7 L of 50% NaOH solution was added to a 50 L reactor, and 1.07 kg of α-chitosan powder was added in batches with stirring. Under nitrogen protection, the mixture was heated to 60 °C and reacted for 4 h. The reaction was stopped, cooled, and then diluted with water. After stirring for 0.5 h, the mixture was centrifuged and filtered. After rinsing with water, 2.7 kg of crude wet α-chitosan (degree of deacetylation approximately 90.3%) was obtained.

[0104] 10.7 L of 50% NaOH solution was added to a 50 L reactor. The crude wet α-chitosan was added in batches with stirring. Under nitrogen protection, the mixture was heated to 60 °C and reacted for 4 h. The reaction was stopped, cooled, and diluted with water. After stirring for 0.5 h, the mixture was centrifuged and filtered. After rinsing with water, 1.58 kg of crude wet α-chitosan was obtained. The wet product was transferred to a vacuum drying oven to obtain highly deacetylated α-chitosan. 623 g of α-chitosan sample 1-1 was collected, with a molecular weight of 313.1 kDa.

[0105] Add 528 ml of 2% acetic acid solution and 1650 ml of 1.6% hydrogen peroxide solution to a 3L three-necked flask. While stirring, add 150 g of α-chitosan sample 1-1 in batches. After the addition is complete, stir and heat to 45℃ to obtain a gel-like viscous solution. Incubate at this temperature for 3 hours. Stop heating and transfer the reaction solution to a 10L reactor. Monitor the initial pH to 5, add 10% sodium hydroxide solution to adjust the pH to 10, add 5 L of anhydrous ethanol for 20 min extraction, centrifuge and filter the reaction solution, add 500 ml of ethanol for rinsing, transfer the wet product to a 10L reactor, and slurry with 2.5 L of anhydrous ethanol for 1 hour. Centrifuge and filter again to obtain 278 g of oligo-α-chitosan wet product. Transfer to a vacuum drying oven to dry, obtaining 112 g of α-chitosan sample 1 with a degree of deacetylation of 82.8% and a molecular weight of 9.83 kDa.

[0106] Example 2 Preparation of α-Chitosan Sample 2

[0107] 1100 ml of 2% hydrogen peroxide solution was added to a 3L three-necked flask. While stirring, 100 g of α-chitosan sample 1-1 was added in batches. After the addition was complete, the mixture was stirred and heated to 65℃ to obtain a gel-like viscous solution. The reaction was maintained at this temperature for 3 hours. Heating was stopped, and the reaction solution was transferred to a 5L beaker. The initial pH was monitored to be 7. 3L of anhydrous ethanol was added for extraction for 20 minutes. The reaction solution was centrifuged and filtered, and then washed with 1000 ml of ethanol to obtain 118.7 g of wet oligo-chitosan. This was then transferred to a vacuum drying oven and dried to obtain 82.8 g of α-chitosan sample 2, with a degree of deacetylation of 91.2% and a molecular weight of 39.2 kDa.

[0108] Example 3 Preparation of α-Chitosan Sample 4

[0109] 1800 ml of 0.3% hydrochloric acid solution was added to a 3L three-necked flask. While stirring, 100 g of α-chitosan sample 1-1 was added in batches. After the addition was complete, the mixture was stirred and heated to 55℃ to obtain a gel-like viscous solution. Then, 3 ml of 30% hydrogen peroxide solution was added dropwise. After the addition was complete, the mixture was kept at this temperature for 3 hours. Heating was stopped, and 2.2 kg of water was added and stirred to dilute the solution. The diluted solution was then transferred to a 10L reactor, and the pH was adjusted to 10 with 10% sodium hydroxide solution. The solution was centrifuged and filtered. The wet product was transferred to a vacuum drying oven and dried to obtain 77 g of α-chitosan sample 4, with a degree of deacetylation of 94.3% and a molecular weight of 136.3 kDa.

[0110] Example 4 Preparation of α-Chitosan Sample 5

[0111] The starting material was α-chitosan. The α-chitosan was pulverized, and the pulverized α-chitosan powder was sieved to obtain uniform α-chitosan powder. 20L of 50% NaOH solution was added to a 50L reactor, and 2.0kg of α-chitosan powder was added in batches with stirring. Under nitrogen protection, the mixture was heated to 50℃ and reacted for 4 hours. The reaction was stopped, cooled, and then diluted with 32L of water. The mixture was stirred for 0.5 hours, centrifuged, filtered, and rinsed with 13.4L of water to obtain 4.95kg of crude α-chitosan wet product (degree of deacetylation approximately 91.2%).

[0112] 20L of 50% NaOH solution was added to a 50L reactor. 4.95kg of crude α-chitosan (wet product) was added in batches with stirring. Under nitrogen protection, the mixture was heated to 50℃ and reacted for 4 hours. The reaction was stopped, cooled, and then diluted with 32L of water. The mixture was stirred for 0.5 hours, centrifuged, filtered, and rinsed with 12.5L of water to obtain 4.153kg of crude α-chitosan (wet product). The wet product was passed through a 16-mesh sieve to prevent agglomeration. The wet product was then transferred to a vacuum drying oven to obtain 1.3kg of α-chitosan sample 5, with a degree of deacetylation of 96.8% and a molecular weight of 332 kDa.

[0113] Example 5 Preparation of α-Chitosan Sample 3

[0114] 1800 ml of 3% hydrochloric acid solution was added to a 3L three-necked flask. 100 g of α-chitosan sample 5 was added in batches with stirring. After the addition was complete, the mixture was stirred and heated to 60℃ to obtain a gel-like viscous solution. 7.5 ml of 30% hydrogen peroxide solution was then added dropwise. After the addition was complete, the mixture was kept at this temperature for 4 hours. Heating was stopped, and 2.2 kg of water was added and stirred to dilute the solution. The diluted solution was then transferred to a 10L reactor. 10% sodium hydroxide solution was added to adjust the pH to 7. The reaction solution was centrifuged and filtered. Water was added to rinse until the rinsing solution was neutral. The wet product was then transferred to a 10L reactor, and 3 L of ethanol was added. The mixture was stirred at 20-30℃ for 1 hour. After centrifugation and filtration again, 378 g of oligo-α-chitosan wet product was obtained. This was transferred to a vacuum drying oven and dried to obtain 77.5 g of α-chitosan sample 3, with a degree of deacetylation of 94.3% and a molecular weight of 80.3 kDa.

[0115] Example 6 Preparation of α-Chitosan Sample B

[0116] 3.6 L of 3% hydrochloric acid solution was added to a 10 L reactor. 200 g of α-chitosan sample 5 was added in batches with stirring. After the addition was complete, the mixture was stirred and heated to 70 °C to obtain a gel-like viscous solution. 24 ml of 30% hydrogen peroxide solution was then added dropwise. After the addition was complete, the mixture was kept at this temperature for 2 h. Heating was stopped, and 4.4 kg of water was added and stirred to dilute the solution. The diluted solution was then transferred to a 20 L reactor. The initial pH was monitored as 6. 10% sodium hydroxide solution was added to adjust the pH to 8. The reaction solution was centrifuged and filtered. Water was added to rinse until the rinsing solution was neutral. The wet product was then transferred to a 10 L reactor, and 5 L of ethanol was added. The mixture was stirred at 20-30 °C for 3 h. After centrifugation and filtration again, 956 g of oligo-α-chitosan wet product was obtained. This was then transferred to a vacuum drying oven to dry, yielding 164 g of α-chitosan sample B with a degree of deacetylation of 95.2% and a molecular weight of 73 kDa.

[0117] Example 7 Preparation of α-Chitosan Sample C

[0118] 1800 ml of 0.1% hydrochloric acid solution was added to a 3L three-necked flask. 100 g of α-chitosan sample 5 was added in batches with stirring. After the addition was complete, the mixture was stirred and heated to 50℃ to obtain a gel-like viscous solution. 4.5 ml of 30% hydrogen peroxide solution was then added dropwise. After the addition was complete, the mixture was kept at this temperature for 5 hours. Heating was stopped, and 2.2 kg of water was added and stirred to dilute the solution. The diluted solution was then transferred to a 10L reactor. 10% sodium hydroxide solution was added to adjust the pH to 7. The reaction solution was centrifuged and filtered. Water was added to rinse until the rinsing solution was neutral. The wet product was then transferred to a 5L beaker, and 2 L of ethanol was added. The mixture was stirred at 20-30℃ for 0.3 hours. After centrifugation and filtration again, 623 g of oligo-α-chitosan wet product was obtained. This product was then transferred to a vacuum drying oven and dried to obtain 76.7 g of α-chitosan sample C, with a degree of deacetylation of 93.5% and a molecular weight of 108 kDa.

[0119] The molecular weight and degree of deacetylation of α-chitosan samples 1, 2, 3, 4, 5, B and C are shown in Table 1 below.

[0120] Table 1. Molecular weight and degree of deacetylation of α-chitosan samples

[0121]

[0122] The powder X-ray diffraction patterns of α-chitosan samples 1, 2, 3, 4, 5, B, and C are basically as follows: Figure 1 As shown, the X-ray diffraction pattern confirmed it to be α-chitosan.

[0123] Example 8 Preparation of β-Chitosan Sample 1

[0124] The starting material is squid bone. First, the squid bone is crushed and sieved to obtain uniform squid bone powder. 39L of 6% hydrochloric acid solution is added to a 50L reactor, and 2.62kg of squid bone powder is added in batches with stirring. The reaction is carried out at 20-30℃ for 5 hours with stirring. The reaction is then stopped, and the reaction solution is centrifuged and filtered to obtain 5.79kg of wet product. 33.8L of 10% sodium hydroxide solution is added to a 50L reactor, and the decalcified wet product is added with stirring. The temperature is raised to 80℃, and the reaction is carried out for 1 hour. Heating is stopped, and after cooling, the reaction solution is centrifuged and filtered to obtain the wet product. 33.8L of 10% sodium hydroxide solution is added to a 50L reactor, and the sieved wet product is added with stirring. The temperature is raised to 80℃, and the reaction is carried out for 1 hour. After stopping heating and cooling, the reaction solution was centrifuged and filtered. Water was added to wash the solution until it was nearly neutral, yielding 2.82 kg of wet β-chitosan. This was dried at 50-60°C with forced air until the moisture content was ≤10%, yielding 791 g of β-chitosan. 7.7 L of 50% sodium hydroxide solution was added to a 20 L reactor, and 770 g of β-chitosan was added in batches with stirring. Under nitrogen protection, the temperature was raised to 60°C, and the reaction was carried out for 4 hours. After stopping heating and cooling, 12 L of water was added to dilute the solution, and the diluted solution was centrifuged and filtered. 2075 g of wet product was obtained after filtration. 7.7 L of 50% sodium hydroxide solution was added to a 20 L reactor, and the wet product was added in batches with stirring. Under nitrogen protection, the temperature was raised to 60°C, and the reaction was carried out for 4 hours. Stop heating, cool down, add 12L of water to dilute, centrifuge and filter the diluted solution, rinse with water until neutral, to obtain 1700g of wet product, and dry to obtain 570g of β-chitosan sample 1-1 with a molecular weight of 317.8 kDa.

[0125] 1800 ml of 0.2% hydrochloric acid solution was added to a 3L three-necked flask. While stirring, 100 g of β-chitosan sample 1-1 was added in batches. After the addition was complete, the mixture was stirred and heated to 40℃ to obtain a gel-like viscous solution. 1 ml of 30% hydrogen peroxide solution was then added dropwise. After the addition was complete, the mixture was kept at this temperature for 1 hour. Heating was stopped, and 1.5 kg of water was added and stirred to dilute the solution. The diluted solution was then transferred to a 5L beaker. The initial pH was monitored to be 5. 10% sodium hydroxide solution was added to adjust the pH to 11. The reaction solution was centrifuged and filtered. Water was added to rinse until the rinsing solution was neutral. The wet product was then transferred to a 5L beaker, and 2.5 L of ethanol was added. The mixture was stirred at 20-30℃ for 1 hour. After centrifugation and filtration again, 342 g of oligo-β-chitosan wet product was obtained. This was then transferred to a vacuum drying oven to dry, yielding 60 g of β-chitosan sample 1 with a degree of deacetylation of 90.6% and a molecular weight of 11.6 kDa.

[0126] Example 9 Preparation of β-Chitosan Sample 2

[0127] 1440 ml of 1% hydrochloric acid solution was added to a 3L three-necked flask. 80 g of β-chitosan sample 1-1 was added in batches with stirring. After the addition was complete, the mixture was stirred and heated to 35℃ to obtain a gel-like viscous solution. 1.5 ml of 30% hydrogen peroxide solution was then added dropwise. After the addition was complete, the mixture was kept at this temperature for 1 hour. Heating was stopped, and 1.5 kg of water was added for dilution and stirring. The diluted reaction solution was transferred to a 5L beaker. The initial pH was monitored at 5.66. 10% sodium hydroxide solution was added to adjust the pH to 7. The reaction solution was centrifuged and filtered. After rinsing with water until neutral, the wet product was transferred to a 5L beaker, and 2 L of ethanol was added. The mixture was stirred at 20-30℃ for 0.5 hours. After centrifugation and filtration again, 514 g of oligo-β-chitosan wet product was obtained. This was transferred to a vacuum drying oven and dried to obtain 77.5 g of β-chitosan sample 2, with a degree of deacetylation of 96.8% and a molecular weight of 35.56 kDa.

[0128] Example 10 Preparation of β-Chitosan Sample 4

[0129] The starting material was squid bone. First, the squid bone was crushed and sieved to obtain uniformly sized squid bone powder. 33L of 6% hydrochloric acid solution was added to a 50L reactor, and 2.2kg of squid bone powder was added in batches with stirring. The reaction was carried out at 20-30℃ for 1 hour. The reaction was stopped, and the reaction solution was centrifuged and filtered. After rinsing with 11L of water, the filter cake was collected to obtain decalcified wet product. 28.6L of 10% sodium hydroxide solution was added to a 50L reactor, and the decalcified wet product was added with stirring. The temperature was raised to 100℃, and the reaction was carried out for 1 hour. Heating was stopped, and after cooling, the reaction solution was centrifuged and filtered. Water was added and washed until the wash solution was nearly neutral to obtain β-chitoxin wet product. This was dried at 50-60℃ with forced air until the moisture content was ≤10%, yielding 660g of β-chitoxin. Add 6.6 L of 50% sodium hydroxide solution to a 20 L reactor, and add 660 g of β-chitosan in batches with stirring. Under nitrogen protection, heat to 60 °C and react for 3 h. Stop heating, cool, and add 10 L of water to dilute. Centrifuge and filter the diluted solution. After filtration, obtain the wet product. Add 6.6 L of 50% sodium hydroxide solution to a 20 L reactor, and add the wet product in batches with stirring. Under nitrogen protection, heat to 60 °C and react for 3 h. Stop heating, cool, and add 10 L of water to dilute. Centrifuge and filter the diluted solution, and rinse with water until neutral to obtain 1374 g of wet product. Pass the wet product through a 16 mesh sieve and dry in a forced-air oven at 50-60 °C until the moisture content is ≤10%. Collect 490 g of highly deacetylated β-chitosan sample 4, with a deacetylation degree >98% and a molecular weight of 324 kDa.

[0130] Example 11 Preparation of β-Chitosan Sample 3

[0131] 1620 ml of 1% hydrochloric acid solution was added to a 3L three-necked flask. 90 g of β-chitosan sample 4 was added in batches with stirring. After the addition was complete, the mixture was stirred and heated to 35℃ to obtain a gel-like viscous solution. 0.7 ml of 30% hydrogen peroxide solution was then added dropwise. After the addition was complete, the mixture was kept at this temperature for 1 hour. Heating was stopped, and 1.5 kg of water was added for dilution and stirring. The diluted reaction solution was transferred to a 5L beaker. The initial pH was monitored as 4. 10% sodium hydroxide solution was added to adjust the pH to 11. The reaction solution was centrifuged and filtered. After rinsing with water until neutral, the wet product was transferred to a 5L beaker, and 2 L of ethanol was added. The mixture was stirred at 20-30℃ for 2 hours. After centrifugation and filtration again, 446 g of oligochitosan wet product was obtained. This product was then transferred to a vacuum drying oven to dry, yielding 60 g of β-chitosan sample 3 with a degree of deacetylation >98% and a molecular weight of 80.8 kDa.

[0132] The molecular weight and degree of deacetylation of β-chitosan samples 1, 2, 3 and 4 are shown in Table 2 below.

[0133] Table 2. Molecular weight and degree of deacetylation of β-chitosan samples

[0134]

[0135] The powder X-ray diffraction patterns of β-chitosan samples 1, 2, 3, and 4 are basically as follows: Figure 2 As shown, the X-ray diffraction pattern confirmed it to be β-chitosan.

[0136] Animal Experiment 1: Preventive Effect of α-Chitosan on Acute Gastric Mucosal Injury in Mice

[0137] Animal experiments:

[0138] Grouping: After 3 days of acclimatization, mice were randomly divided into 10 groups (6 mice / group): blank group, model group, sucralfate group, Huoweisu group (Huoweisu brand Deerle capsules), Jiuwei group (Jiuwei brand chitosan capsules), and α-chitosan sample groups 1, 2, 3, 4, and 5.

[0139] Administration: Each dose group was administered the drug by gavage at a fixed time for 7 consecutive days. Each mouse was given 10 mL / kg of the drug solution (all administered at clinically equivalent doses). The control group and model group (pure water), sucralfate group (56 mg / mL), oxytocin group (34 mg / mL), glutathione group (36 mg / mL), and α-chitosan groups 1, 2, 3, 4, and 5 (36 mg / mL) were included. The daily weight changes of the mice were recorded.

[0140] Fasting: Fasting is allowed for 24 hours after the last dose of medication, but water intake is permitted.

[0141] Modeling: Except for the blank group, all other groups were administered anhydrous ethanol by gavage at a dose of 10 mL / kg (administered the drug before modeling).

[0142] Sacrifice: 1 h after modeling, mice were sacrificed, their intact stomachs were exposed, the pylorus was ligated, and they were infused with 10% formalin solution and fixed for 20 min.

[0143] Stomach removal: After fixation, cut along the greater curvature of the stomach, wash away the stomach contents, and unfold the gastric mucosa;

[0144] Measurement: The length and width of the bleeding point or bleeding band are measured visually using vernier calipers to assess gastric mucosal damage.

[0145] The degree of gastric mucosal injury is expressed by the injury incidence rate (%), injury score index and injury inhibition rate, and is calculated according to (1)-(4) as follows. The scoring criteria are shown in Table 1-1 below:

[0146] Table 1-1 Scoring Criteria for Gastric Mucosal Injury

[0147]

[0148] Total score = Bleeding point score + Length score + Width score × 2 (1) (where: because the severity of the injury represented by the width is higher than that of the length, the score is doubled)

[0149] Incidence of injury = Number of rats in a group that developed hemorrhage or ulceration / Number of rats in the group × 100% (2)

[0150] Injury score index = Sum of injury scores for each group / Number of animals in each group (3)

[0151] Damage inhibition rate = (damage score of model group - damage score of experimental group) / damage score of model group × 100% (4)

[0152] Pathological histological observation and scoring:

[0153] The gastric mucosa of each mouse was excised from the site of injury, fixed with 10% formalin solution, routinely prepared into slides, and stained with H&E to observe the area including the entire mucosal layer. The injury was classified into 5 grades based on the cumulative extent of congestion, hemorrhage, and mucosal cell degeneration and necrosis throughout the mucosal epithelial layer. The weight of congestion was 1, the weight of hemorrhage was 2, and the weight of epithelial cell degeneration and necrosis was 3. The total score of the lesion was calculated according to formula (5), and the scoring criteria are shown in Table 1-2 below.

[0154] Table 1-2 Scoring Criteria for Gastric Mucosal Lesions

[0155]

[0156] Total lesion score = congestion score + hemorrhage score × 2 + epithelial cell degeneration and necrosis score × 3 (5)

[0157] Data processing: Data are expressed as mean ± standard deviation. Statistical analysis was performed using SPSS 25.0 software, employing one-way ANOVA. A p-value < 0.05 was considered statistically significant.

[0158] Experimental results

[0159] 1. Outcome of gastric mucosal injury

[0160] (1) All drug administration groups showed milder damage than the model group. Among the α-chitosan samples, α-chitosan sample 3 showed the most significant preventive effect against anhydrous ethanol-induced gastric mucosal damage in mice.

[0161] (2) The results of the assessment of gastric mucosal injury are shown in Table 1-3. The α-chitosan sample group had the lowest incidence of gastric mucosal injury and the smallest injury score index.

[0162] Table 1-3 Assessment Results of Gastric Mucosal Injury

[0163]

[0164] Compared with the blank group, Compared with the model group, ^P < 0.05, ^^P < 0.01; compared with the sucralfate group, Compared with the Deerle capsule group, Compared with the Jiuwei capsule group, .

[0165] Among the five α-chitosan samples, α-chitosan sample 3 and α-chitosan sample 4 showed good preventive effects against anhydrous ethanol-induced gastric mucosal damage in mice.

[0166] Compared with the model group, the total lesion scores of each experimental group were significantly reduced, indicating that the positive control drug and α-chitosan samples 1 to 5 all had a preventive and protective effect on the gastric mucosa. α-chitosan samples 3 and 4 showed milder gastric mucosal damage in mice, suggesting that α-chitosan samples 3 and 4 may have a good preventive effect against anhydrous ethanol-induced gastric mucosal damage in mice; among them, α-chitosan sample 3 showed the strongest preventive effect against anhydrous ethanol-induced gastric mucosal damage in mice.

[0167] Animal Experiment 2: Preventive Effect of β-Chitosan Samples on Acute Gastric Mucosal Injury in Mice

[0168] Animal experiments:

[0169] Grouping: After 3 days of acclimatization, mice were randomly divided into 9 groups (6 mice / group): blank group, model group, sucralfate group, active ingredient group, Jiuwei group, and β-chitosan sample groups 1, 2, 3, and 4.

[0170] Administration: Each dose group was administered the drug via gavage at a fixed time for 7 consecutive days. Each mouse was given 10 mL / kg of the drug solution (all administered at clinically equivalent doses). The control group and model group (pure water), sucralfate group (56 mg / mL), oxytocin group (34 mg / mL), β-chitosan group (36 mg / mL), and β-chitosan sample groups 1, 2, 3, and 4 (36 mg / mL) were included. The daily weight changes of the mice were recorded.

[0171] The procedures for fasting, modeling, euthanasia, stomach removal, and measurement, as well as the methods for gastric mucosal injury scoring, pathological histological observation and scoring, and data processing, were conducted in accordance with Animal Experiment 1.

[0172] Experimental results

[0173] 1. Outcome of gastric mucosal injury

[0174] (1) Results of gastric mucosal injury showed that the damage in all treatment groups was reduced compared with that in the model group. Among the β-chitosan samples, the β-chitosan sample group 2 had the most significant preventive effect on gastric mucosal injury induced by anhydrous ethanol in mice.

[0175] (2) The results of the assessment of gastric mucosal injury are shown in Table 2-1. The β-chitosan sample group had the lowest incidence of gastric mucosal injury and the smallest injury score index.

[0176] Table 2-1 Assessment Results of Gastric Mucosal Injury

[0177]

[0178] Compared with the blank group, Compared with the model group, ^^P<0.01; compared with the sucralfate group, Compared with the Deerle capsule group, Compared with the Jiuwei capsule group, .

[0179] Among the four β-chitosan samples, β-chitosan sample 2 showed the best inhibitory effect. Compared with the model group, the total lesion score of each experimental group was significantly reduced, indicating that the positive control drug and β-chitosan samples 1-4 all have a preventive and protective effect on the gastric mucosa.

[0180] β-Chitosan samples 1-4 all showed good preventive effects, among which β-chitosan sample 2 showed the strongest preventive effect against anhydrous ethanol-induced gastric mucosal damage in mice.

[0181] Animal Experiment 3: Preventive Effects of α- and β-Chitosan Samples on Acute Gastric Mucosal Injury in Mice

[0182] Animal experiments:

[0183] Grouping: After 7 days of acclimatization, mice were randomly divided into 5 groups (6 mice / group): blank group (K group), model group (M group), Jiuwei group (J group), β-chitosan sample group 2 (A group), and α-chitosan sample group C (C group).

[0184] Drug administration: Mice in each group were administered 10 mL / kg via gavage at a fixed time each day (all at clinically equivalent doses) for 14 consecutive days. The daily weight changes of mice were recorded in groups K (pure water), M (pure water), J (36 mg / mL), A (36 mg / mL), and C (36 mg / mL).

[0185] The procedures for fasting, modeling, euthanasia, stomach removal, and measurement, as well as the methods for gastric mucosal injury scoring, pathological histological observation and scoring, and data processing, were conducted in accordance with Animal Experiment 1.

[0186] Experimental results

[0187] 1. Outcome of gastric mucosal injury

[0188] (1) Results of gastric mucosal injury showed that all treatment groups had reduced damage compared with group M (model group). Among the chitosan samples, α-chitosan sample C had the most significant preventive effect on acute gastric mucosal injury induced by anhydrous ethanol in mice.

[0189] (2) The results of the assessment of gastric mucosal injury are shown in Table 3-1. Compared with the model group, both β-chitosan sample 2 (A) and α-chitosan sample C can reduce the incidence of injury, reduce the injury score index, and increase the injury inhibition rate. The differences are significant (P<0.001 or P<0.05). Among them, α-chitosan sample C has the lowest incidence of gastric mucosal injury, the smallest injury score index, and the highest injury inhibition rate. Moreover, the injury inhibition rate is significantly better than that of the positive drug Jiuwei chitosan (P<0.05).

[0190] Table 3-1 Assessment results of gastric mucosal injury (Mean±SD)

[0191]

[0192] Compared to group M, Compared with group J, ^P < 0.05

[0193] The histopathological scores of gastric mucosal injury in mice are shown in Table 3-2. Compared with group M (model group), the total lesion scores of each treatment group were significantly reduced, indicating that the positive control drug Jiuwei chitosan and β-chitosan sample 2 and α-chitosan sample C all have certain preventive and protective effects on the gastric mucosa. In addition, compared with the positive control drug Jiuwei chitosan, β-chitosan sample 2 and α-chitosan sample C have better preventive effects on anhydrous ethanol-induced acute gastric mucosal injury in mice, and the preventive effect of α-chitosan sample C is the strongest.

[0194] Table 3-2 Histopathological Scoring Table for Gastric Mucosal Injury in Mice (Mean ± SD, n = 6)

[0195]

[0196] Compared to group M, Compared with group J, ^P < 0.05

[0197] Animal Experiment 4: Effects of α- and β-chitosan samples on the treatment of chronic gastric ulcer model

[0198] animal experiments

[0199] Adaptation feeding: Healthy male Wistar rats were acclimatized for 7 days;

[0200] Modeling and Grouping: The acetic acid injection method was used to establish the model. Animals were fasted for 24 hours but allowed free access to water. After anesthesia with sodium pentobarbital, the abdomen was disinfected, and the abdominal cavity was incised below the xiphoid process. The stomach was gently pulled out of the abdominal cavity, and 25 μL of 30% glacial acetic acid was injected subserosively at the pylorus using a micro-syringe. The incision was sutured, and the animals were fed and watered normally postoperatively. On the second day, rats in good condition after surgery were randomly divided into four groups according to body weight: Group M (model group), Group J (positive control, Jiuwei chitosan group), Group A (β-chitosan sample group 2), and Group C (α-chitosan sample group C). Group K (blank group) rats underwent parallel operation with 30% glacial acetic acid replaced by physiological saline. Each group consisted of 10 rats.

[0201] Drug administration: On the second day after modeling, rats in each group were administered the drug (10 mL / kg) by gavage at a fixed time every day for 14 consecutive days. Group K (pure water), Group M (pure water), Group J (24 mg / mL), Group A (24 mg / mL), and Group C (24 mg / mL) were divided into four groups. The daily weight changes of the rats were recorded.

[0202] Sample collection: After the last administration, the patient was fasted for 24 hours but allowed free access to water, and then sacrificed. The entire stomach was removed and immersed in a 10% formalin solution for 20 minutes. After immersion, the stomach was cut open along the greater curvature, and the contents were washed away. The proventriculus was taken, spread out and laid flat on a glass plate. The moisture in the ulcer was absorbed with paper, and its area and volume were measured.

[0203] Ulcer area and volume measurement:

[0204] Count the number of squares occupied by the ulcer under a dissecting microscope with a scale, and convert it into area. Then, inject black ink into the ulcer using a microsyringe to fill it and level it with the surrounding area. The volume of the ulcer is the reading on the microsyringe.

[0205] Data processing:

[0206] Data are expressed as mean ± standard deviation. Statistical analysis was performed using SPSS 25.0 software, employing one-way ANOVA. A p-value < 0.05 was considered statistically significant.

[0207] Experimental results:

[0208] (1) Results of ulcer damage

[0209] The stomachs of rats in group K (blank group) were normal, while the stomachs of rats in the other groups showed varying degrees of ulceration. Among them, group C (α-chitosan sample group C) had the lowest degree of ulceration.

[0210] (2) Results of ulcer area and volume analysis

[0211] ① As shown in Table 4-1, the ulcer area of ​​each treatment group was significantly reduced compared with group M (model group). Among them, group C (α-chitosan sample group C) had the smallest ulcer area, and the difference was statistically significant (P<0.05). Group C (α-chitosan sample group C) was significantly different from group J (positive drug, Jiuwei chitosan group) (P<0.05). ② As shown in Table 4-1, the ulcer volume of each treatment group was reduced compared with group M (model group). Among them, group C (α-chitosan sample group C) had the smallest ulcer volume, and the difference was statistically significant (P<0.05). Furthermore, group C (α-chitosan sample group C) was significantly different from group J (positive drug, Jiuwei chitosan group) (P<0.05).

[0212] Table 4-1 Ulcer area and volume in rats (Mean ± SD, n = 10)

[0213]

[0214] Compared to group M, Compared with group J, ^P < 0.05

[0215] Both β-chitosan sample 2 and α-chitosan sample C can reduce the ulcer area and volume in rats with chronic gastric ulcers to some extent. Compared with Jiuwei capsules and other chitosan samples, α-chitosan sample C has a better therapeutic effect on acetic acid-induced gastric mucosal damage in rats.

[0216] Animal Experiment 5: Preventive Effect of α-Chitosan Samples on Acute Gastric Mucosal Injury in Mice

[0217] Animal experiments:

[0218] Grouping: After 3 days of acclimatization, mice were randomly divided into 4 groups (6 mice / group): blank group, model group, 3 groups of α-chitosan samples, and α-chitosan D (molecular weight 80.6 kDa, degree of deacetylation 88.7%) group.

[0219] Administration: Each dose group was administered the drug via gavage at a fixed time for 7 consecutive days. Each mouse was given 10 mL / kg of the drug solution. The control group and model group (pure water), α-chitosan group 3 (36 mg / mL), and α-chitosan group D (36 mg / mL) were also included. The daily weight changes of the mice were recorded.

[0220] The procedures for fasting, modeling, euthanasia, stomach removal, and measurement, as well as the methods for gastric mucosal injury scoring, pathological histological observation and scoring, and data processing, were conducted in accordance with Animal Experiment 1.

[0221] Experimental results

[0222] 1. Outcome of gastric mucosal injury

[0223] The results of the gastric mucosal injury assessment are shown in Table 5-1. The incidence of gastric mucosal injury and the gastric mucosal injury score index of α-chitosan sample group 3 were significantly lower than those of α-chitosan sample D.

[0224] Table 5-1 Assessment Results of Gastric Mucosal Injury

[0225]

[0226] Compared with the blank group, Compared with the model group, .

Claims

1. A chitosan, characterized in that, The chitosan possesses at least one of the following characteristics: (1) The molecular weight of the chitosan is 5-400 kDa; (2) Deacetylation degree greater than 85%; (3) The chitosan is α-chitosan or β-chitosan; (4) The chitosan is used to prepare products for the prevention or treatment of gastrointestinal mucosal damage.

2. The chitosan according to claim 1, characterized in that, The chitosan possesses at least one of the following characteristics: (1) The molecular weight of the chitosan is 10-300 kDa; (2) Deacetylation degree greater than 90%; (3) The chitosan is α-chitosan or β-chitosan; (4) The chitosan is used to prepare products for the prevention or treatment of gastrointestinal mucosal damage.

3. The chitosan according to claim 1, wherein the chitosan is α-chitosan with a molecular weight of 60-200 kDa; preferably, the chitosan is selected from those with a molecular weight of 70-140 kDa; more preferably, the chitosan is selected from those with a molecular weight of 80-140 kDa.

4. The chitosan according to claim 1, wherein the chitosan is β-chitosan with a molecular weight of 10-350 kDa; preferably, the chitosan is selected from those with a molecular weight of 20-100 kDa; more preferably, the chitosan has a molecular weight of 20-50 kDa.

5. The chitosan according to claim 1, wherein the chitosan has the following characteristics: (1) The molecular weight of the chitosan is 70-140 kDa; (2) Deacetylation degree greater than 90%; (3) The chitosan is α-chitosan; (4) The chitosan is used to prepare products for the prevention or treatment of gastrointestinal mucosal damage.

6. The chitosan according to claim 1, wherein the chitosan has the following characteristics: (1) The molecular weight of the chitosan is 20-100 kDa; (2) Deacetylation degree greater than 90%; (3) The chitosan is β-chitosan; (4) The chitosan is used to prepare products for the prevention or treatment of gastrointestinal mucosal damage.

7. The use of an α-chitosan in the preparation of products for the prevention or treatment of gastrointestinal mucosal damage, wherein the α-chitosan has a molecular weight of 70-140 kDa and a degree of deacetylation greater than 90%.

8. The use of a β-chitosan in the preparation of products for the prevention or treatment of gastrointestinal mucosal damage, wherein the β-chitosan has a molecular weight of 20-100 kDa and a degree of deacetylation greater than 90%.

9. The chitosan or its use according to any one of claims 1-8, wherein, The diseases mentioned include acute gastric mucosal injury, gastritis, gastric ulcer, intestinal mucosal injury, duodenal ulcer, enteritis, ulcerative colitis, or digestive system ulcer.

10. The chitosan or its use according to any one of claims 1-8, wherein the product is a pharmaceutical, health product, or food.

11. A method for preparing chitosan according to claim 1, characterized in that, The method includes the following steps: reacting high molecular weight chitosan with peroxide in an acidic solution to obtain the product.

12. The preparation method according to claim 11, wherein the acidic solution is a hydrochloric acid solution with a concentration of 6.0% or less; preferably, the hydrochloric acid concentration is 5.0% or less; more preferably, the hydrochloric acid concentration is 4.0% or less.

13. The preparation method according to claim 11, wherein the reaction time is 0.5-6.0 hours, preferably 1.0-5.0 hours.

14. The preparation method according to claim 11, wherein the reaction temperature is 30-80℃, preferably 35-70℃.

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